Schonbeck, Christian; Holm, Rene; Westh, Peter; Peters, Gunther H.
Extending the hydrophobic cavity of beta-cyclodextrin results in more negative heat capacity changes but reduced binding affinities
JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY, 78:351-361, APR 2014

The formation of inclusion complexes of hydroxypropylated beta-cyclodextrins (CDs) with three bile salts are investigated to shed light on the role played by the hydroxypropyl (HP) substituents. The HP-chains are situated at the rim of the CD and may thus extend the hydrophobic cavity of the CD. Calorimetric titrations in a broad temperature range and molecular dynamics simulations confirm previous speculations that the HP-chains cause an increase in dehydrated nonpolar surface area upon formation of the complexes. This additional burial of nonpolar surface area, 12-16 angstrom(2) per HP-chain according to the MD simulations, results in more negative values of Delta C-p degrees, which are in quantitative agreement with what is expected for hydrophobic dehydration. Although these observations support the picture of an extended hydrophobic cavity, HP beta CD complexes were less stable than their unsubstituted counterparts. This indicates that increased hydrophobic contacts are not always accompanied by increased binding strength. The linear dependence of Delta C-p degrees, Delta H degrees and Delta S degrees on the number of HP-chains give rise to isoentropic and isoenthalpic temperatures at which Delta H degrees and Delta S degrees are independent of the number of HP-chains on the host CD (but depend on the type of bile salt). Interestingly, these convergence temperatures are close to what is observed for unfolding of proteins and may be a common feature of hydrophobic dehydration.

DOI:10.1007/s10847-013-0305-2

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